Stress-associated neuroinflammation

Stress-associated neuroinflammation is the research theme behind Arborwake's central story. The project's research review sums it up in one line: different stress models change microglia, neurons, vessels and blood immune signals through distinct and partly independent routes.

In the brain#

The points below follow the project's 29 October review. They describe animal models unless stated.

• Stress is not inflammation. Stress hormones and noradrenaline signalling are not automatically inflammation or injury.
• A changed shape is not a diagnosis. Microglial shape, movement and gene activity are different measures from cytokine release.
• Priming needs a second challenge. Frank et al. (2012) stressed rats, then exposed their isolated microglia to a bacterial molecule (LPS). The earlier stress made the later response stronger, partly through glucocorticoids. The second challenge is part of the result.
• History can last, then fade. In a mouse social-defeat model, some changes resolved within days and others lasted to about 24 days (Weber et al., 2019; Wohleb et al., 2014).
• Not everything is microglial. Some neural outcomes continued after microglia were removed.
• Microglia can protect. Removing microglial BDNF made mice more susceptible to some stress effects (Woodburn et al., 2023).
• Humans are uncertain. The review's public claim is: "Certain experimental stress paradigms change brain–immune communication in rodents. The translation to everyday human stress remains uncertain."

In the game#

• No stress meter. The review warns that a single "stress inflammation" meter would misrepresent the evidence.
• Pressure and aftermath. STRESS_STORY.md separates the outside pressure from a response that can outlast it. Zero inflammation is never the win condition; working function is.
• Same symptom, different cause. Acts I to III repeat this idea across rooms. See Arborwake: The Long Wake.
• Priming only with a challenge. Scene III4 must not call a resting region "primed" unless a prior exposure and a later challenge exist.
• Recovery is real. Act IV has good days, so stress does not always lead to a worse stage.

Development#

• The user made stress-associated neuroinflammation the centre of the story on 29 October, withdrawing the Breach-first plan. See Withdrawn story directions.
• STRESS_STORY.md on main is a revised design recommendation, not approved implementation.
• The research review is a targeted critical review, not a systematic review. Parts of it rest on abstracts.

See also#

• Stress-associated neurovascular relay
• Science guardrails
• Microglia

Sources#

1. .GAME_PLAN/ARBORWAKE_STRESS_NEUROIMMUNE_RESEARCH_REVIEW_2026-10-29.md (working copy, not in Git)
2. .GAME_PLAN/ARBORWAKE_THE_LONG_WAKE_COMPLETE_GAME_PLAN_v0.5.md (working copy, not in Git)
3. 1ded4c01c:docs/integrated-design-v2/STRESS_STORY.mdcopy
4. 1ded4c01c:AGENTS.mdcopy